JP2009097965A - Specimen transfer device to nuclear magnetic resonance device and nuclear magnetic resonance device - Google Patents

Specimen transfer device to nuclear magnetic resonance device and nuclear magnetic resonance device Download PDF

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JP2009097965A
JP2009097965A JP2007269220A JP2007269220A JP2009097965A JP 2009097965 A JP2009097965 A JP 2009097965A JP 2007269220 A JP2007269220 A JP 2007269220A JP 2007269220 A JP2007269220 A JP 2007269220A JP 2009097965 A JP2009097965 A JP 2009097965A
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sample
transfer channel
stopper
extrusion solvent
sample transfer
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JP5049732B2 (en
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Minseok Park
ミンソク 朴
Michiya Okada
道哉 岡田
Isao Kitagawa
功 北川
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Hitachi Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/28Details of apparatus provided for in groups G01R33/44 - G01R33/64
    • G01R33/30Sample handling arrangements, e.g. sample cells, spinning mechanisms
    • G01R33/307Sample handling arrangements, e.g. sample cells, spinning mechanisms specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer

Abstract

<P>PROBLEM TO BE SOLVED: To provide a specimen transfer device and an NMR device wherein a problem is solved that specimen molecules in a specimen solution diffuse up to an extrusion solvent to lower the concentration of the specimen molecules in a detection space, the problem being an inadequacy in a technique for transporting a specimen solution to a detection space of the NMR device by using an extrusion solvent, and also a problem is solved that it takes time to transfer a specimen solution, the problem being an inadequacy in a method for transferring the specimen solution by using gas. <P>SOLUTION: A movable wall is provided across a transfer duct for the specimen solution. The specimen solution is transferred to the detection space by means of the extrusion solvent with the movable wall between. Further, a stopper preventing the movable wall from moving is provided in the specimen transfer channel in order that the specimen solution is accurately transferred to the detection space. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

本発明は、液体の試料を核磁気共鳴装置の検出空間に移送するための試料移送装置に係り、また、試料移送装置を備えた核磁気共鳴装置に関する。   The present invention relates to a sample transfer apparatus for transferring a liquid sample to a detection space of a nuclear magnetic resonance apparatus, and also relates to a nuclear magnetic resonance apparatus provided with the sample transfer apparatus.

核磁気共鳴(Nuclear Magnetic Resonance、以下、NMR)装置は、強い静磁場を作る磁石の中の検出空間に置かれた試料分子に一連の高周波の交流磁場パターンを照射し、試料分子内の核スピンに摂動を与え、該核スピンの応答を測定する装置である。様々な交流磁場パターンに対する核スピンの応答を解析することにより、分子の構造および分子のダイナミックス、分子間相互作用を解析することができる。NMR装置を用いた分析手法は、試料分子を破壊する必要がない点と、試料分子を結晶化する必要がない点で、他の分析手法にない特長を持つ。   The Nuclear Magnetic Resonance (hereinafter referred to as NMR) apparatus irradiates a sample molecule placed in a detection space in a magnet that creates a strong static magnetic field with a series of high-frequency alternating magnetic field patterns, thereby causing nuclear spins in the sample molecule to be irradiated. Is a device for measuring the response of the nuclear spin. By analyzing the nuclear spin response to various AC magnetic field patterns, the molecular structure, molecular dynamics, and intermolecular interactions can be analyzed. An analysis method using an NMR apparatus has features that are not found in other analysis methods in that it does not require destruction of sample molecules and does not require crystallization of sample molecules.

NMR分析手法の以上の特長は、創薬研究に特に適している。創薬研究では、人体を構成するタンパク質と薬との相互作用を人体に近い環境で計測することが好ましい。NMR分析手法は、人体環境に近い試料溶媒、例えば塩濃度を調整した水にタンパク質の試料分子を溶かした試料溶液を用意し、この試料溶液に薬を投入して測定することができる。また、NMR測定に使ったタンパク質は、破壊されないため、回収して再利用することもできる。この点は、高価で入手困難なタンパク質を試料分子に用いる測定において有利である。   The above features of the NMR analysis technique are particularly suitable for drug discovery research. In drug discovery research, it is preferable to measure the interaction between proteins and drugs that constitute the human body in an environment close to the human body. The NMR analysis method can be measured by preparing a sample solution in which a sample molecule of a protein is dissolved in a sample solvent close to the human body environment, for example, water having a adjusted salt concentration, and putting a drug into this sample solution. Moreover, since the protein used for NMR measurement is not destroyed, it can be recovered and reused. This point is advantageous in measurement using expensive and difficult to obtain proteins as sample molecules.

試料溶液を使ったNMR測定の効率を上げる方法として、フローNMR(flow NMR)装置が考案されている。例えば、特許文献1には、磁石の外部から磁石中の検出空間に繋がる試料移送流路を形成し、磁石外部から試料溶液を該流路に注入し、更に押出し溶媒を注入することで試料溶液を検出空間に移送する、フローNMR装置が開示されている。   As a method for increasing the efficiency of NMR measurement using a sample solution, a flow NMR (flow NMR) apparatus has been devised. For example, in Patent Document 1, a sample transfer channel connected from the outside of a magnet to a detection space in the magnet is formed, a sample solution is injected into the channel from the outside of the magnet, and an extrusion solvent is further injected into the sample solution. A flow NMR apparatus is disclosed that transports the gas to the detection space.

しかし、押出し溶媒を用いて試料を検出空間に移送する方法には、試料溶液中の試料分子が押出し溶媒にまで拡散し、検出空間中の試料分子の濃度が低下するという問題がある。検出空間中の試料分子濃度が低下すると、NMR装置が検出する応答信号が弱くなり、解析結果の誤差を増大させる。   However, the method of transferring the sample to the detection space using the extrusion solvent has a problem that the sample molecules in the sample solution diffuse to the extrusion solvent and the concentration of the sample molecules in the detection space decreases. When the sample molecule concentration in the detection space decreases, the response signal detected by the NMR apparatus becomes weak, and the error of the analysis result increases.

特許文献2には、試料溶液の押出しにガスを用いることで、試料分子が押出し溶媒に拡散する問題を解決する技術が開示されている。特許文献2によれば、試料移送流路の検出空間の前方と後方に2個のガス圧力源を設け、2個のガス圧力源間の圧力差を調整することで、試料溶液が検出空間へ移送される。   Patent Document 2 discloses a technique for solving the problem of sample molecules diffusing into an extrusion solvent by using a gas for extrusion of a sample solution. According to Patent Document 2, two gas pressure sources are provided in front of and behind the detection space of the sample transfer channel, and the pressure difference between the two gas pressure sources is adjusted, so that the sample solution is moved to the detection space. Be transported.

特表2004−534958号公報JP-T-2004-534958 特開平10−90383号公報Japanese Patent Laid-Open No. 10-90383

しかし、試料溶液の移送にガスを使う方法は、移送に時間が掛かる点で問題がある。ガスを利用すると移送に時間が掛かる理由の一つは、ガスの圧縮率が液体より非常に高く、ガス圧力により試料溶液の位置を正確に決めることが難しいことである。   However, the method of using gas for transferring the sample solution has a problem in that it takes time to transfer. One of the reasons why it takes a long time to transfer the gas is that the compressibility of the gas is much higher than that of the liquid and it is difficult to accurately determine the position of the sample solution by the gas pressure.

NMR装置において、試料溶液を正確に検出空間に位置させることは、応答信号の強度と、該信号の分解能の両面から重要である。応答信号の強度は、試料溶液中の全試料分子が検出用アンテナの所定検出空間内に存在する時に最大になる。もし、試料溶液の一部でも検出空間から外れたら、応答信号の強度は低下する。応答信号の分解能は、試料溶液内における静磁場強度が均一な時に最良となる。NMR装置の磁石装置は検出空間内で最も均一な静磁場を作るように製作されるため、試料溶液が検出空間に正確に位置した場合に、最良の信号分解能が得られる。   In the NMR apparatus, accurately positioning the sample solution in the detection space is important in terms of both the intensity of the response signal and the resolution of the signal. The intensity of the response signal is maximized when all sample molecules in the sample solution are present in the predetermined detection space of the detection antenna. If even a part of the sample solution deviates from the detection space, the response signal intensity decreases. The resolution of the response signal is best when the static magnetic field strength in the sample solution is uniform. Since the magnet apparatus of the NMR apparatus is manufactured so as to create the most uniform static magnetic field in the detection space, the best signal resolution can be obtained when the sample solution is accurately positioned in the detection space.

特許文献2の従来技術では、試料溶液を検出空間に正確に位置させるために、流路に沿って試料溶液の位置を検出するセンサーと、該センサーからの信号を処理してガス圧力源を調整する信号プロセッサを設けている。しかし、ガスの高い圧縮率のため、信号の検出とガス圧力源の調整は数回繰り返し行う必要があり、試料溶液を検出空間に位置させるまでに時間が掛かる。   In the prior art of Patent Document 2, in order to accurately position the sample solution in the detection space, a sensor that detects the position of the sample solution along the flow path and a signal from the sensor are processed to adjust the gas pressure source. A signal processor is provided. However, because of the high compression ratio of the gas, it is necessary to repeatedly detect the signal and adjust the gas pressure source several times, and it takes time to position the sample solution in the detection space.

ガスを利用すると試料溶液の移送に時間が掛かるもう一つの理由は、ガスの圧力を高く設定てきない点にある。   Another reason that it takes time to transfer the sample solution when using gas is that the gas pressure cannot be set high.

ガスの圧力を高くすると、ガスと試料溶液との界面が不安定になり、試料溶液の中にガスの泡が発生する。泡は、検出空間内の試料体積を減らし信号強度を弱くする。また、ガスと試料溶液の磁化率の差により泡の面に沿って磁化が発生し、検出空間内の静磁場均一度を低下させ、信号の分解能を劣化させる。さらに、ガスの圧力を高くすると、ガスが試料溶液に溶解され、試料分子のエネルギー散逸を速める問題も発生する。試料分子のエネルギー散逸が速くなると、信号の減衰が速くなり、解析の誤差要因となる。   When the gas pressure is increased, the interface between the gas and the sample solution becomes unstable, and gas bubbles are generated in the sample solution. Foam reduces the sample volume in the detection space and weakens the signal intensity. Also, magnetization is generated along the bubble surface due to the difference in magnetic susceptibility between the gas and the sample solution, reducing the static magnetic field uniformity in the detection space and degrading the signal resolution. Furthermore, when the pressure of the gas is increased, the gas is dissolved in the sample solution, causing a problem that the energy dissipation of the sample molecules is accelerated. When the energy dissipation of the sample molecules increases, the signal decays faster, which causes an error in analysis.

試料溶液の移送に時間が掛かることは、分子のダイナミックスや分子間の相互作用に関わるNMR測定の場合に、特に問題になる。   It takes a long time to transfer the sample solution, especially in the case of NMR measurement related to molecular dynamics and interaction between molecules.

NMR測定の対象となる分子ダイナミックスには、例えば、プロテイン・フォールディング(Protein Folding)がある。プロテイン・フォールディングとは、1次元のペプチド連鎖からなるタンパク質が折りたたまれて固有の3次元構造になる過程であり、タンパク質の構成要素となるペプチドの順番とタンパク質の3次元構造との間の関係を究明する上で重要である。   An example of molecular dynamics to be measured by NMR is protein folding. Protein folding is a process in which a protein consisting of a one-dimensional peptide chain is folded into a unique three-dimensional structure. The relationship between the order of peptides that constitute a protein and the three-dimensional structure of the protein It is important to investigate.

分子のダイナミックスがNMR測定に関わるもう一つの例は、動的核磁化(Dynamic Nulcear Polarization、以下、DNP)現象を利用する測定である。DNPは、核スピンに比べ磁化率が数百万倍以上高い電子スピンを磁化させると、核スピンと電子スピン間の相互作用により電子スピンの磁化が核スピンに移る現象である。DNPにより核スピンの磁化は一時的に熱平衡状態より1万倍以上にも達し、NMR信号の強度を1万倍以上向上させるという報告もある。ただし、DNPによる核スピンの磁化は一時的であり、時間と共に熱平衡状態の値に戻る。従って、DNPによるNMR信号強度向上効果を利用するためには、DNP現象を起こしてからNMR測定を行うまでの時間経過を短縮することが重要である。   Another example in which molecular dynamics is related to NMR measurement is measurement using a dynamic nuclear polarization (hereinafter DNP) phenomenon. DNP is a phenomenon in which when an electron spin whose magnetic susceptibility is several million times higher than that of a nuclear spin is magnetized, the magnetization of the electron spin is transferred to the nuclear spin by the interaction between the nuclear spin and the electron spin. There is a report that the nuclear spin magnetization temporarily reaches 10,000 times or more from the thermal equilibrium state by DNP, and the intensity of the NMR signal is improved by 10,000 times or more. However, the magnetization of the nuclear spin by DNP is temporary and returns to the value of the thermal equilibrium state with time. Therefore, in order to utilize the effect of improving the NMR signal intensity by DNP, it is important to shorten the time elapsed from the occurrence of the DNP phenomenon until the NMR measurement is performed.

以上のように、試料溶液の移送に押出し溶媒を用いる従来方法では、試料溶液中の試料分子が押出し溶媒にまで拡散する問題があり、一方、ガスを用いる方法では試料の移送に時間が掛かるという問題がある。   As described above, in the conventional method using an extrusion solvent for transferring a sample solution, there is a problem that sample molecules in the sample solution diffuse to the extrusion solvent. On the other hand, in the method using gas, it takes time to transfer the sample. There's a problem.

本発明の目的は、押出し溶媒を用いて試料溶液をNMR装置の検出空間に移送する技術を改良して、試料溶液中の試料分子が押出し溶媒にまで拡散し検出空間中の試料分子の濃度を低下させる問題点を解決し、もってガスを用いて試料溶液を移送する方法の課題である移送に時間が掛かる点をも解決した試料移送装置およびNMR装置を提供することにある。   The purpose of the present invention is to improve the technology for transferring the sample solution to the detection space of the NMR apparatus using the extrusion solvent, so that the sample molecules in the sample solution diffuse to the extrusion solvent and the concentration of the sample molecules in the detection space is reduced. An object of the present invention is to provide a sample transfer apparatus and an NMR apparatus that solve the problem of lowering and solve the problem that the transfer takes time, which is a problem of the method of transferring a sample solution using a gas.

本発明の試料移送装置は、試料溶液と押出し溶媒との間に可動壁を設け、この可動壁によって試料溶液中の試料分子が押出し溶媒にまで拡散するのを防止するようにしたことにある。   In the sample transfer device of the present invention, a movable wall is provided between the sample solution and the extrusion solvent, and the movable wall prevents the sample molecules in the sample solution from diffusing into the extrusion solvent.

詳細には、NMR装置における磁石装置の内孔を通り、プローブの検出アンテナの位置にまで試料溶液を移送する試料移送流路を有し、その試料移送流路に可動壁と、該可動壁の移動範囲を設定する第1ストッパおよび第2ストッパを備える。試料移送流路の一方の端部近傍には試料注入部を接続し、また、その試料注入部から試料移送流路に注入された試料溶液を押出し溶媒によって前記検出アンテナに向けて押出す押出し溶媒ポンプと、その押出し溶媒ポンプに接続された押出し溶媒容器を備える。試料移送流路の他方の端部には排出ガスポンプおよび排出ガス容器を接続する。また、試料注入部と押出し溶媒ポンプおよび排出ガスポンプを制御する試料移送制御部を備える。第1ストッパは試料移送流路内の前記試料注入部と前記押出し溶媒ポンプとの間に設け、第2ストッパは前記検出アンテナの近傍に設ける。   Specifically, it has a sample transfer channel that transfers the sample solution to the position of the detection antenna of the probe through the inner hole of the magnet device in the NMR apparatus, a movable wall in the sample transfer channel, A first stopper and a second stopper for setting the movement range are provided. An extrusion solvent for connecting a sample injection part in the vicinity of one end of the sample transfer channel, and for extruding the sample solution injected from the sample injection part into the sample transfer channel toward the detection antenna by an extrusion solvent A pump and an extrusion solvent container connected to the extrusion solvent pump are provided. An exhaust gas pump and an exhaust gas container are connected to the other end of the sample transfer channel. A sample transfer control unit that controls the sample injection unit, the extrusion solvent pump, and the exhaust gas pump is also provided. The first stopper is provided between the sample injection portion in the sample transfer channel and the extrusion solvent pump, and the second stopper is provided in the vicinity of the detection antenna.

以上の装置構成により、押出し溶媒ポンプと排出ガスポンプとの圧力差で、可動壁が第1ストッパと第2ストッパとの間を往復するようになり、これにより試料移送流路に注入された試料溶液が可動壁を介して試料押し出し溶媒により検出アンテナの位置にまで移送され、また、検出アンテナの位置から試料注入部に返送されるようになる。   With the above apparatus configuration, the movable wall reciprocates between the first stopper and the second stopper due to the pressure difference between the extrusion solvent pump and the exhaust gas pump, and thereby the sample solution injected into the sample transfer channel. Is transferred to the position of the detection antenna by the sample extrusion solvent through the movable wall, and is returned from the position of the detection antenna to the sample injection portion.

本発明のNMR装置は、下記の3つの態様を含む。   The NMR apparatus of the present invention includes the following three aspects.

第1の態様では、静磁場を作る磁石装置に縦方向と横方向の2つの室温ボアが設けられる。この2つの室温ボアのうち一方にプローブが挿入され、プローブの前記磁石装置の中心部に近い先端部に検出アンテナが配置される。プローブは高周波信号ケーブルにより計測装置に接続される。前記縦方向の室温ボアには、そのボアを貫通するように試料移送流路が配置される。   In the first aspect, the magnet device for generating a static magnetic field is provided with two room temperature bores in the vertical direction and the horizontal direction. A probe is inserted into one of the two room temperature bores, and a detection antenna is disposed at the tip of the probe near the center of the magnet device. The probe is connected to the measuring device by a high-frequency signal cable. A sample transfer channel is disposed in the longitudinal room temperature bore so as to penetrate the bore.

試料移送流路の下方の端部近傍には試料注入部が接続され、さらに、試料注入部から試料移送流路に注入された試料溶液を押出し溶媒によって前記検出アンテナに向けて押出す押出し溶媒ポンプが接続される。押出し溶媒ポンプは押出し溶媒容器と接続される。試料移送流路の他端には排出ガスポンプおよび排出ガス容器が接続される。また、試料注入部と押出し溶媒ポンプおよび排出ガスポンプを制御する試料移送制御部が設けられる。   A sample injection unit is connected to the vicinity of the lower end of the sample transfer channel, and further an extrusion solvent pump that extrudes the sample solution injected from the sample injection unit into the sample transfer channel toward the detection antenna by an extrusion solvent Is connected. The extrusion solvent pump is connected to the extrusion solvent container. An exhaust gas pump and an exhaust gas container are connected to the other end of the sample transfer channel. In addition, a sample transfer control unit that controls the sample injection unit, the extrusion solvent pump, and the exhaust gas pump is provided.

前記試料移送流路における、試料注入部と押出し溶媒ポンプとの間には第1ストッパが設けられ、検出アンテナの近傍には第2ストッパが設けられる。試料移送流路内の第1ストッパと第2ストッパとの間に可動壁が設けられる。   A first stopper is provided between the sample injection portion and the extrusion solvent pump in the sample transfer channel, and a second stopper is provided in the vicinity of the detection antenna. A movable wall is provided between the first stopper and the second stopper in the sample transfer channel.

これにより、押出し溶媒ポンプと排出ガスポンプとの圧力差により、試料移送流路内に設けられた可動壁が第1ストッパと第2ストッパとの間を往復し、試料溶液が可動壁を介して試料押し出し溶媒により検出空間に移送され、また検出空間から試料注入部まで返送されるようになる。   Thereby, due to the pressure difference between the extrusion solvent pump and the exhaust gas pump, the movable wall provided in the sample transfer flow path reciprocates between the first stopper and the second stopper, and the sample solution passes through the movable wall. It is transferred to the detection space by the extrusion solvent and is returned from the detection space to the sample injection section.

第2の態様では、磁石装置に1つの縦方向の室温ボアが設けられる。そして、その室温ボアに検出アンテナを備えたプローブが挿入され、また、室温ボアおよびプローブを貫通して試料移送流路が設けられる。そのほかの構成は前記した第1の態様と同じである。   In the second aspect, the magnet device is provided with one longitudinal room temperature bore. A probe equipped with a detection antenna is inserted into the room temperature bore, and a sample transfer channel is provided through the room temperature bore and the probe. Other configurations are the same as those of the first aspect described above.

第3の態様では、磁石装置に縦方向の室温ボアを含む少なくとも1つの室温ボアが設けられる。室温ボアのいずれか1つに、検出アンテナを有するプローブが挿入され、また、縦方向の室温ボアに試料移送流路が配置される。試料移送流路は検出アンテナを貫通するように挿入され、貫通した後U字に曲げられて、検出アンテナの外部を通り元の位置まで戻るように構成される。そして、試料移送流路の一方の端部側に試料注入部が接続され、更に押出し溶媒ポンプと押出し溶媒容器が接続される。試料移送流路の他方の端部には排出ガスポンプおよび排出ガス容器が接続される。他の構成は、第1の態様及び第2の態様と同じである。   In a third aspect, the magnet device is provided with at least one room temperature bore including a longitudinal room temperature bore. A probe having a detection antenna is inserted into any one of the room temperature bores, and a sample transfer channel is disposed in the room temperature bore in the vertical direction. The sample transfer channel is inserted so as to penetrate the detection antenna, and is bent into a U shape after penetrating the sample transfer channel and passes through the outside of the detection antenna to return to the original position. And a sample injection | pouring part is connected to the one edge part side of a sample transfer flow path, and also an extrusion solvent pump and an extrusion solvent container are connected. An exhaust gas pump and an exhaust gas container are connected to the other end of the sample transfer channel. Other configurations are the same as those in the first and second aspects.

以上の試料移送装置および第1乃至第3の態様のNMR装置において、試料注入部は、バルブの開閉により試料溶液を試料移送流路に注入するように構成されることが望ましい。   In the sample transfer apparatus and the NMR apparatus of the first to third aspects described above, the sample injection section is preferably configured to inject the sample solution into the sample transfer flow path by opening and closing a valve.

本発明の試料移送装置およびNMR装置は、試料溶液の移送にガスの代わりに押出し溶媒を使うため試料移送の時間が短縮され、更に試料溶液と押出し溶媒との間に可動壁があるため、試料溶液中の試料分子が押出し溶媒にまで拡散し検出空間中の試料分子の濃度が低下することを低減できるという効果がある。   Since the sample transfer apparatus and the NMR apparatus of the present invention use an extrusion solvent instead of gas for the transfer of the sample solution, the sample transfer time is shortened, and further, there is a movable wall between the sample solution and the extrusion solvent. There is an effect that it is possible to reduce a decrease in the concentration of the sample molecules in the detection space due to the diffusion of the sample molecules in the solution to the extrusion solvent.

以下、図面を用いて、本発明の試料移送装置およびNMR装置を説明する。   Hereinafter, the sample transfer apparatus and the NMR apparatus of the present invention will be described with reference to the drawings.

図1は、試料移送装置を含むNMR装置の第1の態様を示した構成図である。本実施例のNMR装置は、静磁場を作る磁石装置1に横方向の室温ボア2と縦方向の室温ボア2aが設けられ、プローブ3が室温ボア2に挿入される。磁石装置1の中心部に近いプローブ3の先端部には検出アンテナ4が配置される。計測装置5は、プローブ3と高周波信号ケーブル6により接続される。計測装置5は、NMR信号を取得する際に、高周波信号ケーブル6の経由で高周波の交流磁場パターンをプローブ3に送信し、プローブ3から核スピンの応答信号を高周波信号ケーブル6の経由で受信し、データ処理を行う。処理されたデータは、ユーザーコンピュータ7からユーザーに提供される。   FIG. 1 is a configuration diagram showing a first mode of an NMR apparatus including a sample transfer apparatus. In the NMR apparatus of the present embodiment, a horizontal room temperature bore 2 and a vertical room temperature bore 2 a are provided in a magnet apparatus 1 that generates a static magnetic field, and a probe 3 is inserted into the room temperature bore 2. A detection antenna 4 is disposed at the tip of the probe 3 near the center of the magnet device 1. The measuring device 5 is connected to the probe 3 by a high frequency signal cable 6. When acquiring the NMR signal, the measuring device 5 transmits a high-frequency AC magnetic field pattern to the probe 3 via the high-frequency signal cable 6 and receives a nuclear spin response signal from the probe 3 via the high-frequency signal cable 6. Data processing is performed. The processed data is provided from the user computer 7 to the user.

本発明のNMR装置は、以上の一般的なNMR装置の構成に加え、更に以下の構成を有する。先ず、縦方向の室温ボア2aを貫通して試料移送流路10を配置する。試料移送流路10の一端(以下、第1端部)には、試料注入部11と、押出し溶媒ポンプ12を接続する。また、試料移送流路10のもう一端(以下、第2端部)には、排出ガスポンプ13を接続する。押出し溶媒ポンプ12と排出ガスポンプ13には、各々、押出し溶媒容器14と、排出ガス容器15が接続される。試料注入部11と押出し溶媒ポンプ12と排出ガスポンプ13は、試料移送制御部16により制御される。試料移送制御部16は、計測装置5もしくはユーザーコンピュータ7が兼ねてもよい。   The NMR apparatus of the present invention has the following configuration in addition to the configuration of the above general NMR apparatus. First, the sample transfer channel 10 is disposed through the vertical room temperature bore 2a. A sample injection unit 11 and an extrusion solvent pump 12 are connected to one end (hereinafter referred to as a first end) of the sample transfer channel 10. Further, an exhaust gas pump 13 is connected to the other end (hereinafter referred to as a second end) of the sample transfer channel 10. An extrusion solvent container 14 and an exhaust gas container 15 are connected to the extrusion solvent pump 12 and the exhaust gas pump 13, respectively. The sample injection unit 11, the extrusion solvent pump 12 and the exhaust gas pump 13 are controlled by the sample transfer control unit 16. The sample transfer control unit 16 may also serve as the measuring device 5 or the user computer 7.

図2は、図1の構成において、試料移送流路10と試料注入部11を更に詳しく示した図である。   FIG. 2 is a diagram showing the sample transfer channel 10 and the sample injection unit 11 in more detail in the configuration of FIG.

試料移送流路10の第1端部における試料注入部11と押し出し溶媒ポンプ12との間に第1ストッパ21を設け、検出アンテナ4の近傍の試料移送流路10に第2ストッパ22を設ける。そして、試料移送流路10の第1端部と押出し溶媒ポンプ12の間に可動壁20を設ける。   A first stopper 21 is provided between the sample injection unit 11 and the push solvent pump 12 at the first end of the sample transfer channel 10, and a second stopper 22 is provided in the sample transfer channel 10 in the vicinity of the detection antenna 4. A movable wall 20 is provided between the first end of the sample transfer channel 10 and the extrusion solvent pump 12.

可動壁20は、試料溶液と押出し溶媒を隔離する機能を持ち、可動壁20の両側の圧力差により、試料移送流路10の第1端部に設けた第1ストッパ21から検出空間の近傍に設けた第2ストッパ22まで往復する。   The movable wall 20 has a function of isolating the sample solution and the extrusion solvent. Due to a pressure difference between both sides of the movable wall 20, the movable wall 20 is located near the detection space from the first stopper 21 provided at the first end of the sample transfer channel 10. It reciprocates to the provided second stopper 22.

本実施例では、試料移送流路10の第1端部に、1つ若しくは複数のバルブ23を介して試料注入部11が接続されている。試料注入部11は、1つ若しくは複数の試料容器24と、試料調合容器25と、試料撹拌器26と、シリンジポンプ27と、排出バルブ28と、1つまたは複数の試料排出容器29と、流路切り替え器30と、フィルタ31からなる。   In this embodiment, the sample injection unit 11 is connected to the first end of the sample transfer channel 10 via one or a plurality of valves 23. The sample injection unit 11 includes one or more sample containers 24, a sample preparation container 25, a sample stirrer 26, a syringe pump 27, a discharge valve 28, one or more sample discharge containers 29, a flow It consists of a path switch 30 and a filter 31.

試料容器24はシリンジであり、ユーザーもしくは試料移送制御部16の制御により、内部の試料を試料調合容器25に注入する。試料容器24を複数用いる場合は、各試料容器に、例えば、タンパク質分子を含む高濃度の試料溶液と、塩濃度を調節した水溶媒と、酸性度調節用のバッファ溶液と、前記タンパク質分子との相互作用を調べようとする薬液を格納する。試料溶液の逆流を更に防止するためには、試料容器24と試料調合容器25の間に、バルブ若しくは逆止弁を設けてもよい。試料撹拌器26は、例えば超音波試料撹拌器であり、試料調合容器25中の試料溶液の濃度が均一になるように撹拌する。シリンジポンプ27は、試料調合容器25の圧力を制御し、試料溶液を試料移送流路10に送出する機能と、試料移送流路10から試料溶液を回収する機能を持つ。   The sample container 24 is a syringe, and injects an internal sample into the sample preparation container 25 under the control of the user or the sample transfer control unit 16. When using a plurality of sample containers 24, each sample container includes, for example, a high-concentration sample solution containing protein molecules, an aqueous solvent with adjusted salt concentration, a buffer solution for adjusting acidity, and the protein molecules. Stores the chemical that is going to be examined for interaction. In order to further prevent the backflow of the sample solution, a valve or a check valve may be provided between the sample container 24 and the sample preparation container 25. The sample stirrer 26 is, for example, an ultrasonic sample stirrer, and stirs so that the concentration of the sample solution in the sample preparation container 25 becomes uniform. The syringe pump 27 has a function of controlling the pressure of the sample preparation container 25 to send the sample solution to the sample transfer channel 10 and a function of recovering the sample solution from the sample transfer channel 10.

図3は、試料移送装置がNMR実験時に行う動作を説明する図である。   FIG. 3 is a diagram for explaining the operation performed by the sample transfer apparatus during the NMR experiment.

図3(A)は、NMR実験を開始する前に行う試料調合時の動作を示す。試料移送流路10は、排出ガスポンプ13から注入された排出ガスで満ちている。可動壁20は、押出し溶媒ポンプ12と排出ガスポンプ13の圧力を制御することにより、第1ストッパ21の位置に置かれる。試料移送流路10と試料注入部11の間のバルブ23は閉じた状態にする。試料容器24の中に格納されていた試料は試料調合容器25に注入され、試料撹拌器26により均一濃度を持つ試料溶液となる。シリンジポンプ27は停止状態になる。   FIG. 3A shows the operation during sample preparation performed before starting the NMR experiment. The sample transfer channel 10 is filled with exhaust gas injected from the exhaust gas pump 13. The movable wall 20 is placed at the position of the first stopper 21 by controlling the pressure of the extrusion solvent pump 12 and the exhaust gas pump 13. The valve 23 between the sample transfer channel 10 and the sample injection unit 11 is closed. The sample stored in the sample container 24 is injected into the sample preparation container 25 and becomes a sample solution having a uniform concentration by the sample agitator 26. The syringe pump 27 is stopped.

図3(B)は、調合が終わり、試料溶液を試料移送流路10に注入する時の試料移送装置の動作を示す。試料撹拌器26は動作を停止し、試料容器24は試料溶液が試料調合容器25から逆流しないようにシリンジの位置を固定する。もし、試料容器24と試料調合容器25の間にバルブがあれば、そのバルブを閉める。試料移送流路10と試料注入部11の間のバルブ23を開け、シリンジポンプ27を正圧に制御することで、試料溶液は試料移送流路10に注入される。   FIG. 3B shows the operation of the sample transfer device when the preparation is completed and the sample solution is injected into the sample transfer channel 10. The sample agitator 26 stops operating, and the sample container 24 fixes the position of the syringe so that the sample solution does not flow backward from the sample preparation container 25. If there is a valve between the sample container 24 and the sample preparation container 25, the valve is closed. The sample solution is injected into the sample transfer channel 10 by opening the valve 23 between the sample transfer channel 10 and the sample injection unit 11 and controlling the syringe pump 27 to a positive pressure.

図3(C)は、注入された試料溶液を検出空間に移送する時の試料移送装置の動作を示す。バルブ23を閉め、押出し溶媒ポンプ12と排出ガスポンプ13の圧力を制御し、可動壁20を第1ストッパ21から第2ストッパ22まで移動させる。第2ストッパ22の位置は、試料溶液と排出ガスの界面および試料溶液と可動壁20の界面および可動壁20に発生する磁化が検出空間の静磁場均一度を実質上影響しないように設定する。例えば、検出空間中央において、静磁場強度の変化が1ppb以下であれば、検出空間の静磁場均一度に実質上影響がないと判断できる。   FIG. 3C shows the operation of the sample transfer device when transferring the injected sample solution to the detection space. The valve 23 is closed, the pressures of the extrusion solvent pump 12 and the exhaust gas pump 13 are controlled, and the movable wall 20 is moved from the first stopper 21 to the second stopper 22. The position of the second stopper 22 is set so that the magnetization generated at the interface between the sample solution and the exhaust gas, the interface between the sample solution and the movable wall 20 and the movable wall 20 does not substantially affect the static magnetic field uniformity in the detection space. For example, if the change in the static magnetic field strength is 1 ppb or less at the center of the detection space, it can be determined that there is substantially no influence on the static magnetic field uniformity in the detection space.

試料溶液と押出し溶媒とは、可動壁20により隔離されるため、試料溶液中の試料分子が押出し溶媒にまで拡散し検出空間中の試料分子の濃度が低下するのを防止できる。また、可動壁20を第2ストッパ22の位置で止めることにより、試料溶液を検出空間に正確かつ迅速に位置させることができる。更に、試料溶液の移送に押出し溶媒を使うことと、可動壁20で押出し溶媒と試料溶液を隔離することにより、ガスを用いた押出しで発生する泡の発生やガスの試料溶液への溶解も防止できる。   Since the sample solution and the extrusion solvent are separated by the movable wall 20, it is possible to prevent the sample molecules in the sample solution from diffusing into the extrusion solvent and reducing the concentration of the sample molecules in the detection space. Further, by stopping the movable wall 20 at the position of the second stopper 22, the sample solution can be accurately and quickly positioned in the detection space. Further, by using an extrusion solvent for transferring the sample solution and isolating the extrusion solvent and the sample solution with the movable wall 20, generation of bubbles generated by extrusion using gas and dissolution of the gas into the sample solution are prevented. it can.

図3(D)は、試料溶液を検出空間から試料調合容器25へ回収する時の動作を示す。先ず、押出し溶媒ポンプ12と排出ガスポンプ13の圧力を制御し、可動壁20を第2ストッパ22から第1ストッパ21まで移動させる。次に、バルブ23を開け、シリンジポンプ27を負圧に制御し、試料溶液を試料調合容器25に回収する。   FIG. 3D shows an operation when the sample solution is collected from the detection space to the sample preparation container 25. First, the pressure of the extrusion solvent pump 12 and the exhaust gas pump 13 is controlled to move the movable wall 20 from the second stopper 22 to the first stopper 21. Next, the valve 23 is opened, the syringe pump 27 is controlled to a negative pressure, and the sample solution is collected in the sample preparation container 25.

図3(E)は、試料調合容器25中の試料溶液を排出する時の動作を示す。先ずバルブ23を閉め、排出バルブ28を開ける。シリンジポンプ27を正圧に制御し、試料溶液を試料排出容器29に排出する。試料溶液は、流路、流路切り替え器30により、複数の試料排出容器29の中の1つを選択して排出することができる。複数の試料排出容器29を使えば、排出試料の分析や再利用に有利である。   FIG. 3E shows an operation when the sample solution in the sample preparation container 25 is discharged. First, the valve 23 is closed and the discharge valve 28 is opened. The syringe pump 27 is controlled to a positive pressure, and the sample solution is discharged to the sample discharge container 29. The sample solution can be discharged by selecting one of the plurality of sample discharge containers 29 by the flow path and flow path switch 30. Using a plurality of sample discharge containers 29 is advantageous for analyzing and reusing discharged samples.

排出バルブ28と、流路切り替え器30との間には、分子の寸法に対し選択性を持つフィルタ31が設けられている。この位置にフィルタ31を設けることにより、例えば、寸法の大きいタンパク質分子は試料調合容器25の中に残し、低分子の薬液や試料溶媒のみを試料排出容器29に排出することができる。タンパク質分子を残し、低分子の薬液や試料溶媒のみを排出すれば、試料溶液中のタンパク質分子の濃度を簡単に調整できる効果と、高価なタンパク質分子を簡単に再利用できる効果がある。フィルタ31は、透過させる分子を適宜選択するために、取替えできる構造が望ましい。   Between the discharge valve 28 and the flow path switch 30, a filter 31 having selectivity with respect to the molecular size is provided. By providing the filter 31 at this position, for example, protein molecules having a large size can be left in the sample preparation container 25 and only the low-molecular chemical solution and the sample solvent can be discharged to the sample discharge container 29. If the protein molecules are left and only the low-molecular chemical solution and the sample solvent are discharged, the concentration of the protein molecules in the sample solution can be easily adjusted, and the expensive protein molecules can be easily reused. The filter 31 preferably has a replaceable structure in order to appropriately select molecules to be transmitted.

図には示されていないが、流路切り替え器30と試料排出容器29の間にフィルタを設けてもよい。この構成によれば、複数の試料排出容器29への流路毎に異なるフィルタを設置することができる。該流路毎に、透過させる分子の異なるフィルタを設ければ、流路切り替え器30の設定を変えることで、簡便に透過させる分子を切り替えることができる。   Although not shown in the drawing, a filter may be provided between the flow path switch 30 and the sample discharge container 29. According to this configuration, a different filter can be installed for each flow path to the plurality of sample discharge containers 29. If a filter with different molecules to be permeated is provided for each flow path, the permeated molecules can be easily switched by changing the setting of the flow path switch 30.

試料移送装置は洗浄する必要があり、このために試料容器24に洗浄溶媒を注入する。試料容器24に洗浄溶媒を注入する場合、洗浄溶媒のみを試料調合容器25に注入し、洗浄のため試料撹拌器を運転した後に、図3(B)に示す試料移送流路10への注入、図3(C)に示す検出空間への移送、図3(D))に示す検出空間から試料調合容器25への回収、図3(E)に示す試料排出容器29への排出の順に試料移送装置を動作させる。   The sample transfer device needs to be cleaned. For this purpose, a cleaning solvent is injected into the sample container 24. When injecting the cleaning solvent into the sample container 24, only the cleaning solvent is injected into the sample preparation container 25, and after operating the sample stirrer for cleaning, injection into the sample transfer channel 10 shown in FIG. Transfer of the sample to the detection space shown in FIG. 3C, recovery from the detection space shown in FIG. 3D to the sample preparation container 25, and discharge to the sample discharge container 29 shown in FIG. Operate the device.

本実施例の試料移送装置は、押出し溶媒を使うため試料移送時間の短縮が図れ、しかも、可動壁により、試料溶液と押出し溶媒との混合や分子の拡散を低減できる効果があり、このため、高速で純度の高い試料溶液を検出空間の正確な位置に移送する用途に適する。   The sample transfer apparatus of the present embodiment uses an extrusion solvent, so that the sample transfer time can be shortened, and the movable wall has an effect of reducing the mixing of the sample solution and the extrusion solvent and the diffusion of molecules. It is suitable for use in transferring a sample solution with high purity at high speed to an accurate position in the detection space.

図4は、試料移送装置を含むNMR装置の第2の態様を示した構成図である。静磁場を作る磁石装置201は、縦方向の室温ボア202を有し、プローブ203が室温ボア202に挿入される。プローブ203の中央部には空洞が設けられ、試料移送流路10が該空洞を貫通して配置される。上記の他は、第1の態様のNMR装置と共通する。   FIG. 4 is a configuration diagram showing a second mode of the NMR apparatus including the sample transfer apparatus. The magnet device 201 that creates a static magnetic field has a vertical room temperature bore 202, and a probe 203 is inserted into the room temperature bore 202. A cavity is provided in the center of the probe 203, and the sample transfer channel 10 is disposed through the cavity. Other than the above, the NMR apparatus of the first aspect is common.

以上の構成によれば、室温ボアを1つ有する磁石装置でも、本発明の試料移送装置を適用することができる。   According to the above configuration, the sample transfer device of the present invention can be applied even to a magnet device having one room temperature bore.

図5は、第3の態様のNMR装置における試料移送装置の試料移送流路310の構造を示した図である。第3の態様では、室温ボアは縦方向の1つのみでも良く、また、縦方向と横方向の2つでも良い。試料移送流路310は、縦方向の室温ボア302の中を、検出アンテナ4を貫通して挿入されたのち、U字に曲げられ、検出アンテナ4の外部を通って、試料移送流路310の第1端部と同じ側に出てくる。したがって、試料移送流路310の第1端部と第2端部は、室温ボア302の同じ側に配置される。   FIG. 5 is a diagram showing the structure of the sample transfer channel 310 of the sample transfer apparatus in the NMR apparatus of the third aspect. In the third aspect, the room temperature bore may be only one in the vertical direction, or may be two in the vertical direction and the horizontal direction. The sample transfer channel 310 is inserted into the vertical room temperature bore 302 through the detection antenna 4, bent into a U shape, passes through the outside of the detection antenna 4, and passes through the sample transfer channel 310. Comes out on the same side as the first end. Accordingly, the first end and the second end of the sample transfer channel 310 are disposed on the same side of the room temperature bore 302.

以上の構成によれば、試料移送流路310の長さが実施例1および実施例2のときよりも短くなり、操作性の向上が図れると共に破損の可能性が低減される。   According to the above configuration, the length of the sample transfer channel 310 is shorter than that in the first and second embodiments, so that the operability can be improved and the possibility of breakage is reduced.

試料移送装置を含むNMR装置の第一の実施例を示す装置構成図である。It is an apparatus block diagram which shows the 1st Example of the NMR apparatus containing a sample transfer apparatus. 第一の実施例において、試料移送装置の試料移送流路と試料注入部を詳しく示した構成図である。In the first embodiment, it is a configuration diagram showing in detail a sample transfer flow path and a sample injection portion of the sample transfer device. 第一の実施例において、試料移送装置がNMR実験時に行う動作を説明するもので、試料調合時の状態を示す図である。In a 1st Example, it demonstrates the operation | movement which a sample transfer apparatus performs at the time of NMR experiment, and is a figure which shows the state at the time of sample preparation. 調合が終わり、試料溶液を試料移送流路に移送するときの状態を示す図である。It is a figure which shows a state when mixing is completed and a sample solution is transferred to a sample transfer channel. 注入された試料溶液を検出空間に移送するときの状態を示す図である。It is a figure which shows a state when transferring the injected sample solution to detection space. 試料溶液を検出空間から試料調合容器へ回収するときの状態を示す図である。It is a figure which shows a state when collect | recovering a sample solution from a detection space to a sample preparation container. 試料調合容器中の試料溶液を排出するときの状態を示す図である。It is a figure which shows a state when discharging | emitting the sample solution in a sample preparation container. 試料移送装置を含むNMR装置の第二の実施例を示す装置構成図である。It is an apparatus block diagram which shows the 2nd Example of the NMR apparatus containing a sample transfer apparatus. 試料移送装置の別の例を示す概略構成図である。It is a schematic block diagram which shows another example of a sample transfer apparatus.

符号の説明Explanation of symbols

1…磁石装置、2,2a…室温ボア、3…プローブ、4…検出アンテナ、5…計測装置、6…高周波信号ケーブル、7…ユーザーコンピュータ、10…試料移送流路、11…試料注入部、12…押出し溶媒ポンプ、13…排出ガスポンプ、14…押出し溶媒容器、15…排出ガス容器、16…試料移送制御部、20…可動壁、21…第1ストッパ、22…第2ストッパ、23…バルブ、24…試料容器、201…磁石装置、202…室温ボア、203…プローブ、302…室温ボア、310…試料移送流路。   DESCRIPTION OF SYMBOLS 1 ... Magnet apparatus, 2, 2a ... Room temperature bore, 3 ... Probe, 4 ... Detection antenna, 5 ... Measuring device, 6 ... High frequency signal cable, 7 ... User computer, 10 ... Sample transfer flow path, 11 ... Sample injection part, DESCRIPTION OF SYMBOLS 12 ... Extrusion solvent pump, 13 ... Exhaust gas pump, 14 ... Extrusion solvent container, 15 ... Exhaust gas container, 16 ... Sample transfer control part, 20 ... Movable wall, 21 ... 1st stopper, 22 ... 2nd stopper, 23 ... Valve , 24 ... Sample container, 201 ... Magnet device, 202 ... Room temperature bore, 203 ... Probe, 302 ... Room temperature bore, 310 ... Sample transfer channel.

Claims (8)

核磁気共鳴装置における磁石装置の内孔に配置されたプローブの検出アンテナが設けられている位置に試料溶液を移送するための試料移送装置であって、
前記磁石装置の内孔を通り、前記プローブの検出アンテナが設けられている位置に試料溶液を移送する試料移送流路を有し、
前記試料移送流路の一方の端部側に試料注入部と、前記試料注入部から前記試料移送流路に注入された試料溶液を押出し溶媒によって前記検出アンテナに向けて押出す押出し溶媒ポンプおよび、前記押出し溶媒ポンプに接続された押出し溶媒容器を有し、
前記試料移送流路の他方の端部側に排出ガスポンプおよび排出ガス容器を有し、
前記試料注入部と前記押出し溶媒ポンプおよび前記排出ガスポンプを制御する試料移送制御部を有し、
前記試料移送流路に可動壁と、その可動壁の移動範囲を設定する第1ストッパおよび第2ストッパを有し、
前記第1ストッパを前記試料注入部と前記押出し溶媒ポンプとの間に有し、
前記第2ストッパを前記検出アンテナの近傍に有し、
前記押出し溶媒ポンプと前記排出ガスポンプとの圧力差により、前記可動壁が前記第1ストッパと前記第2ストッパとの間を往復し、これにより試料溶液が前記可動壁を介して前記試料押し出し溶媒により移送されるようにしたことを特徴とする核磁気共鳴装置への試料移送装置。
A sample transfer device for transferring a sample solution to a position where a detection antenna of a probe arranged in an inner hole of a magnet device in a nuclear magnetic resonance apparatus is provided,
Having a sample transfer channel for transferring the sample solution to the position where the detection antenna of the probe is provided through the inner hole of the magnet device
A sample injection unit on one end side of the sample transfer channel, and an extrusion solvent pump for extruding the sample solution injected from the sample injection unit into the sample transfer channel toward the detection antenna by an extrusion solvent; and Having an extrusion solvent container connected to the extrusion solvent pump;
An exhaust gas pump and an exhaust gas container on the other end side of the sample transfer channel;
A sample transfer control unit for controlling the sample injection unit, the extrusion solvent pump, and the exhaust gas pump;
A movable wall and a first stopper and a second stopper for setting a moving range of the movable wall in the sample transfer channel;
Having the first stopper between the sample injection part and the extrusion solvent pump;
Having the second stopper in the vicinity of the detection antenna;
Due to the pressure difference between the extrusion solvent pump and the exhaust gas pump, the movable wall reciprocates between the first stopper and the second stopper, so that the sample solution is moved by the sample extrusion solvent through the movable wall. A sample transfer device to a nuclear magnetic resonance apparatus characterized by being transferred.
前記試料注入部が、バルブの開閉により試料溶液を前記試料移送流路に注入するように構成されていることを特徴とする請求項1に記載の核磁気共鳴装置への試料移送装置。   The sample transfer device to the nuclear magnetic resonance apparatus according to claim 1, wherein the sample injection unit is configured to inject a sample solution into the sample transfer channel by opening and closing a valve. 試料溶液に対して核磁気共鳴測定を行うための装置であって、
縦方向と横方向の2つの室温ボアが設けられた、静磁場を作る磁石装置と、
2つの前記室温ボアのうち一方に挿入されたプローブと、
前記プローブの前記磁石装置の中心部に近い先端部に配置された検出アンテナと、
前記プローブと高周波信号ケーブルにより接続された計測装置と、
前記磁石装置の縦方向の室温ボアを貫通して配置された試料移送流路と、
前記試料移送流路の下方の端部側に接続された試料注入部と、
前記試料注入部から前記試料移送流路に注入された試料溶液を押出し溶媒によって前記検出アンテナに向けて押出す押出し溶媒ポンプおよび、前記押出し溶媒ポンプに接続された押出し溶媒容器と、
前記試料移送流路の他方の端部側に接続された排出ガスポンプおよび排出ガス容器と、
前記試料注入部と前記押出し溶媒ポンプおよび前記排出ガスポンプを制御する試料移送制御部と、
前記試料移送流路における、前記試料注入部と前記押出し溶媒ポンプとの間に設けられた第1ストッパおよび前記検出アンテナの近傍に設けられた第2ストッパと、
前記試料移送流路に設けられ、前記第1ストッパと前記第2ストッパとの間を移動する可動壁とを有し、
前記押出し溶媒ポンプと前記排出ガスポンプとの圧力差により前記可動壁が前記第1ストッパと前記第2ストッパとの間を往復し、これにより試料溶液が前記可動壁を介して前記試料押し出し溶媒により前記検出アンテナの位置に移送され、また試料注入部に返送されるようにしたことを特徴とする核磁気共鳴装置。
An apparatus for performing nuclear magnetic resonance measurement on a sample solution,
A magnet device for creating a static magnetic field provided with two room temperature bores in the longitudinal direction and the transverse direction;
A probe inserted into one of the two room temperature bores;
A detection antenna disposed at the tip of the probe near the center of the magnet device;
A measuring device connected to the probe by a high-frequency signal cable;
A sample transfer channel disposed through a room temperature bore in the longitudinal direction of the magnet device;
A sample injection part connected to the lower end side of the sample transfer channel;
An extrusion solvent pump for extruding the sample solution injected from the sample injection portion into the sample transfer channel toward the detection antenna by an extrusion solvent, and an extrusion solvent container connected to the extrusion solvent pump;
An exhaust gas pump and an exhaust gas container connected to the other end side of the sample transfer channel;
A sample transfer control unit for controlling the sample injection unit, the extrusion solvent pump, and the exhaust gas pump;
A first stopper provided between the sample injection part and the extrusion solvent pump in the sample transfer channel and a second stopper provided in the vicinity of the detection antenna;
A movable wall provided in the sample transfer channel and moving between the first stopper and the second stopper;
Due to the pressure difference between the extrusion solvent pump and the exhaust gas pump, the movable wall reciprocates between the first stopper and the second stopper, whereby the sample solution passes through the movable wall by the sample extrusion solvent. A nuclear magnetic resonance apparatus characterized in that it is transferred to the position of the detection antenna and returned to the sample injection section.
前記試料注入部が、バルブの開閉により試料溶液を前記試料移送流路に注入するように構成されていることを特徴とする請求項3に記載の核磁気共鳴装置。   The nuclear magnetic resonance apparatus according to claim 3, wherein the sample injection unit is configured to inject a sample solution into the sample transfer channel by opening and closing a valve. 試料溶液に対して核磁気共鳴測定を行うための装置であって、
縦方向の室温ボアが設けられた、静磁場を作る磁石装置と、
前記室温ボアに挿入されたプローブと、
前記プローブの前記磁石装置の中心部に近い先端部に配置された検出アンテナと、
前記プローブと高周波信号ケーブルにより接続された計測装置と、
前記室温ボアおよび前記プローブを貫通して配置された試料移送流路と、
前記試料移送流路の下方の端部近傍に接続された試料注入部と、
前記試料注入部から前記試料移送流路に注入された試料溶液を押出し溶媒によって前記検出アンテナに向けて押出す押出し溶媒ポンプおよび、前記押出し溶媒ポンプに接続された押出し溶媒容器と、
前記試料移送流路の他方の端部に接続された排出ガスポンプおよび排出ガス容器と、
前記試料注入部と前記押出し溶媒ポンプおよび前記排出ガスポンプを制御する試料移送制御部と、
前記試料移送流路における前記試料注入部と前記押出し溶媒ポンプとの間に設けられた第1ストッパおよび前記検出アンテナの近傍に設けられた第2ストッパと、
前記試料移送流路に設けられ、前記第1ストッパと前記第2ストッパとの間を移動する可動壁とを有し、
前記押出し溶媒ポンプと前記排出ガスポンプとの圧力差により前記可動壁が前記第1ストッパと前記第2ストッパとの間を往復し、これにより試料溶液が前記可動壁を介して前記試料押し出し溶媒により前記検出アンテナの位置に移送され、また試料注入部に戻されるようにしたことを特徴とする核磁気共鳴装置。
An apparatus for performing nuclear magnetic resonance measurement on a sample solution,
A magnet device that creates a static magnetic field with a vertical room temperature bore;
A probe inserted into the room temperature bore;
A detection antenna disposed at the tip of the probe near the center of the magnet device;
A measuring device connected to the probe by a high-frequency signal cable;
A sample transfer channel disposed through the room temperature bore and the probe;
A sample injection part connected to the vicinity of the lower end of the sample transfer channel;
An extrusion solvent pump for extruding the sample solution injected from the sample injection portion into the sample transfer channel toward the detection antenna by an extrusion solvent, and an extrusion solvent container connected to the extrusion solvent pump;
An exhaust gas pump and an exhaust gas container connected to the other end of the sample transfer channel;
A sample transfer control unit for controlling the sample injection unit, the extrusion solvent pump, and the exhaust gas pump;
A first stopper provided between the sample injection portion and the extrusion solvent pump in the sample transfer channel and a second stopper provided in the vicinity of the detection antenna;
A movable wall provided in the sample transfer channel and moving between the first stopper and the second stopper;
Due to the pressure difference between the extrusion solvent pump and the exhaust gas pump, the movable wall reciprocates between the first stopper and the second stopper, whereby the sample solution passes through the movable wall by the sample extrusion solvent. A nuclear magnetic resonance apparatus characterized in that it is transferred to the position of the detection antenna and returned to the sample injection section.
前記試料注入部が、バルブの開閉により試料溶液を前記試料移送流路に注入するように構成されていることを特徴とする請求項5に記載の核磁気共鳴装置。   The nuclear magnetic resonance apparatus according to claim 5, wherein the sample injection unit is configured to inject a sample solution into the sample transfer channel by opening and closing a valve. 試料溶液に対して核磁気共鳴測定を行うための装置であって、
縦方向の室温ボアを含む少なくとも1つの室温ボアが設けられた、静磁場を作る磁石装置と、
前記室温ボアのいずれか1つに挿入されたプローブと、
前記プローブの前記磁石装置の中心部に近い先端部に配置された検出アンテナと、
前記プローブと高周波信号ケーブルにより接続された計測装置と、
前記磁石装置の前記縦方向の室温ボアを通して前記検出アンテナを貫通するように挿入され、前記検出アンテナを貫通後U字に曲げられて前記検出アンテナの外部を通り元の位置まで戻るように配置された試料移送流路と、
前記試料移送流路の一方の端部近傍に接続された試料注入部と、
前記試料注入部から前記試料移送流路に注入された試料溶液を押出し溶媒によって前記検出アンテナに向けて押出す押出し溶媒ポンプおよび、前記押出し溶媒ポンプに接続された押出し溶媒容器と、
前記試料移送流路の他方の端部に接続された排出ガスポンプおよび排出ガス容器と、
前記試料注入部と前記押出し溶媒ポンプおよび前記排出ガスポンプを制御する試料移送制御部と、
前記試料移送流路の前記試料注入部と前記押出し溶媒ポンプとの間に設けられた第1ストッパおよび前記検出アンテナの近傍に設けられた第2ストッパと、
前記試料移送流路に設けられ、前記第1ストッパと前記第2ストッパとの間を移動する可動壁とを有し、
前記押出し溶媒ポンプと前記排出ガスポンプとの圧力差により前記可動壁が前記第1ストッパと前記第2ストッパとの間を往復し、これにより試料溶液が前記可動壁を介して前記試料押し出し溶媒により前記検出アンテナの位置に移送され、また試料注入部に戻されるようにしたことを特徴とする核磁気共鳴装置。
An apparatus for performing nuclear magnetic resonance measurement on a sample solution,
A magnet apparatus for creating a static magnetic field, provided with at least one room temperature bore including a longitudinal room temperature bore;
A probe inserted into any one of the room temperature bores;
A detection antenna disposed at the tip of the probe near the center of the magnet device;
A measuring device connected to the probe by a high-frequency signal cable;
The magnet device is inserted so as to penetrate the detection antenna through the vertical room temperature bore of the magnet device, and is arranged so as to be bent into a U shape after passing through the detection antenna and return to the original position through the outside of the detection antenna. Sample transfer flow path,
A sample injection part connected in the vicinity of one end of the sample transfer channel;
An extrusion solvent pump for extruding the sample solution injected from the sample injection portion into the sample transfer channel toward the detection antenna by an extrusion solvent, and an extrusion solvent container connected to the extrusion solvent pump;
An exhaust gas pump and an exhaust gas container connected to the other end of the sample transfer channel;
A sample transfer control unit for controlling the sample injection unit, the extrusion solvent pump, and the exhaust gas pump;
A first stopper provided between the sample injection portion of the sample transfer channel and the extrusion solvent pump and a second stopper provided in the vicinity of the detection antenna;
A movable wall provided in the sample transfer channel and moving between the first stopper and the second stopper;
Due to the pressure difference between the extrusion solvent pump and the exhaust gas pump, the movable wall reciprocates between the first stopper and the second stopper, whereby the sample solution passes through the movable wall by the sample extrusion solvent. A nuclear magnetic resonance apparatus characterized in that it is transferred to the position of the detection antenna and returned to the sample injection section.
前記試料注入部が、バルブの開閉により試料溶液を前記試料移送流路に注入するように構成されていることを特徴とする請求項7に記載の核磁気共鳴装置。   The nuclear magnetic resonance apparatus according to claim 7, wherein the sample injection unit is configured to inject a sample solution into the sample transfer channel by opening and closing a valve.
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JPH1090383A (en) * 1996-06-14 1998-04-10 Varian Assoc Inc Sample delivery apparatus used in cehmical analysis making use of pressure gas for conveyance of sample
JP2001059827A (en) * 1999-08-23 2001-03-06 Jeol Ltd Liquid chromatography nmr method
JP2002139558A (en) * 2000-10-31 2002-05-17 Shimadzu Corp Nuclear magnetic resonance apparatus
JP2006046968A (en) * 2004-07-30 2006-02-16 Japan Science & Technology Agency Low-temperature flow high-speed nmr measurement method and low-temperature flow high-speed injection nmr
JP2007147312A (en) * 2005-11-24 2007-06-14 Hitachi Ltd Nmr device

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1090383A (en) * 1996-06-14 1998-04-10 Varian Assoc Inc Sample delivery apparatus used in cehmical analysis making use of pressure gas for conveyance of sample
JP2001059827A (en) * 1999-08-23 2001-03-06 Jeol Ltd Liquid chromatography nmr method
JP2002139558A (en) * 2000-10-31 2002-05-17 Shimadzu Corp Nuclear magnetic resonance apparatus
JP2006046968A (en) * 2004-07-30 2006-02-16 Japan Science & Technology Agency Low-temperature flow high-speed nmr measurement method and low-temperature flow high-speed injection nmr
JP2007147312A (en) * 2005-11-24 2007-06-14 Hitachi Ltd Nmr device

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